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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer-reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Primary mutagenicity screening of food additives currently used in Japan
Author:
M. Ishidate Jr, T. Sofuni, K. Yoshikawa, M. Hayashi, T. Nohmi, M. Sawada, A. Matsuoka
Year:
1984
Bibliographic source:
Food and Chemical Toxicology Volume 22, Issue 8, August 1984, Pages 623-636

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
A salmonella/microsome test (Ames tests) was performed on Ethyl butyrate to evaluate the mutagenic effect.
GLP compliance:
not specified
Type of assay:
bacterial gene mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl butyrate
EC Number:
203-306-4
EC Name:
Ethyl butyrate
Cas Number:
105-54-4
Molecular formula:
C6H12O2
IUPAC Name:
ethyl butyrate
Details on test material:
- Name of test material (as cited in study report): Ethyl butyrate
- Molecular formula (if other than submission substance): C6H12O2
- Molecular weight (if other than submission substance): 116.16 mg/kg
- Substance type: Organic
- Physical state: Colorless liquid
- Purity: 99.8%
- Impurities (identity and concentrations):0.2%
Specific details on test material used for the study:
- Name of test material: Ethyl butyrate
- IUPAC name: Ethyl butyrate
- Molecular formula: C6H12O2
- Molecular weight: 116.16 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: 99.8%
- Impurities (identity and concentrations):0.2%

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA92, TA1535,TA100, TA1537, TA94 and TA98
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data available
Metabolic activation:
with and without
Metabolic activation system:
The liver microsome fraction (S-9) was prepared from the liver of Fischer rats
Test concentrations with justification for top dose:
Six different concentrations were used with 10 mg/plate as the maximum concentration.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The chemical was soluble in DMSO
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Details on test system and experimental conditions:
METHOD OF APPLICATION: Preincubation

DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: Duplicate

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other: No data available

OTHER: No data available
Rationale for test conditions:
No data available
Evaluation criteria:
The result was considered positive if the number of colonies found was twice the number in the control (exposed to the appropriate solvent or untreated).
Statistics:
No data available

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA92, TA1535,TA100, TA1537, TA94 and TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
The maximum dose for negative results represents the highest non-cytotoxic dose used in the experiment.

Applicant's summary and conclusion

Conclusions:
Ethyl butyrate failed to induce a doubling of revertant colonies over the control using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.
Executive summary:

A gene mutation toxicity study was performed to determine the mutagenic nature of Ethyl butyrate. The study was performed using Salmonella typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with and without S9 metabolic activation system. The test was performed as per the preincubation assay at six different concentration with 10mg/plate being the maximum concentration. Preincubation was performed for 20 mins and the exposure duration was for 48 hrs. The result was considered positive if the number of colonies found was twice the number in the control (exposed to the appropriate solvent or untreated). Ethyl butyrate failed to induce a doubling of revertant colonies over the control using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 in the presence and absence of S9 metabolic activation system. Hence, Ethyl butyrate is not likely to classify as a gene mutant in vitro.